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Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95

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Abstract

The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes synaptic receptors, ion channels, structural proteins, and signaling molecules required for normal synaptic transmission and synaptic function. The scaffolding and hub protein postsynaptic density protein-95 (PSD-95) is a major element of central chemical synapses and interacts with glutamate receptors, cell adhesion molecules, and cytoskeletal elements. In fact, PSD-95 can regulate basal synaptic stability as well as the activity-dependent structural plasticity of the PSD and, therefore, of the excitatory chemical synapse. Several studies have shown that PSD-95 is highly enriched at excitatory synapses and have identified multiple protein structural domains and protein-protein interactions that mediate PSD-95 function and trafficking to the postsynaptic region. PSD-95 is also a target of several signaling pathways that induce posttranslational modifications, including palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation; these modifications determine the synaptic stability and function of PSD-95 and thus regulate the fates of individual dendritic spines in the nervous system. In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes.

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Acknowledgments

This work was supported by grants from the Basal Center of Excellence in Aging and Regeneration (CONICYT-PFB 12/2007) and FONDECYT (No. 1120156) to N. C. Inestrosa. D. Vallejo and J. F. Codocedo were postdoctoral fellows of CARE. We also thank the Sociedad Química y Minera de Chile (SQM) for a special grant on “The Effects of Lithium on Health and Disease”.

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  1. Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, P. O. Box 114-D, Santiago, Chile

    Daniela Vallejo, Juan F. Codocedo & Nibaldo C. Inestrosa

  2. Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia

    Nibaldo C. Inestrosa

  3. Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile

    Nibaldo C. Inestrosa

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  1. Daniela Vallejo
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  2. Juan F. Codocedo
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  3. Nibaldo C. Inestrosa
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Correspondence to Nibaldo C. Inestrosa.

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Vallejo, D., Codocedo, J.F. & Inestrosa, N.C. Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95. Mol Neurobiol 54, 1759–1776 (2017). https://doi.org/10.1007/s12035-016-9745-1

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